Antiviral agents developed to date are mostly non-protein drugs that exhibit superior antiviral activities such as viral adsorption inhibition, viral penetration inhibition, viral uncoating inhibition, transcription (or translation) inhibition of viral nucleic acid (e.g., viral thymidine kinase inhibition, viral reverse transcriptase inhibition, viral polymerase inhibition, and viral mRNA-capping inhibition) and viral protein synthesis inhibition according to the type of viruses infected and that have relatively low toxicity.
There are several patents associated with antiviral drugs. For example, Korean Patent Application No. 10-2001-0021449, targeting viral transcription inhibition, discloses fusion proteins that inhibit expression of RNA on proviral long terminal repeats (LTRs) in a cell nucleus.
U.S. Pat. No. 5,849,800 discloses an amantadine associated with viral uncoating.
U.S. Pat. No. 4,957,924 discloses an acyclovir as an antiviral drug that inhibits biosynthesis of viral nucleic acid. The acyclovir is a medication prepared by modifying a sugar in nucleic acids and is used to treat herpesvirus infections. The acyclovir competes with deoxyguanosine triphosphate (dGTP) and is incorporated into viral DNA, thus terminating DNA replication.
U.S. Pat. Nos. 5,108,993 and 5,026,687 disclose zidovudine and dideoxyinosine, respectively, reverse transcriptase inhibitors used to treat human immunodeficiency virus (HIV) infections.
U.S. Pat. No. 5,962,725 discloses nelfinavir that suppresses activities of HIV proteases to prevent HIV from producing required proteins.
In addition, arildone and pleconaril are known as antiviral drugs that mediate binding of viruses with host cells, followed by penetration and uncoating. These drugs are reported to inhibit uncoating of capsid proteins from RNA genomes.
Trifluorothymidine is known to be a pyrimidine analogue which is introduced into DNA and thus causes growth of mutants during DNA replication. Foscarnet is known to be bound to herpes DNA polymerase to inhibit DNA replication. Ribavirin and neoplanocin A are known to be guanosine and adenosine analogues that inhibit formation of mRNA cap structures to suppress RNA synthesis.
Other antiviral drugs such as saquinavir, ritonavir and indinavir suppress activities of HIV proteases to prevent HIV from producing required proteins.
However, these antiviral drugs have side effects such as an increase in potential infection rates and continuous occurrence of drug-resistant virus strains in a short time (Magden, et al., Appl Microbiol Biotechnol 66:612-621, 2005).
Antibodies, known as immune proteins, are widely used to treat viral diseases. But, clinical use of the antibodies is restricted to passive immunization which involves neutralization mechanism of antibodies against specific viruses. For example, palivizumab was known (Cardenas, et al., Expert Rev Anti Infect Ther 3:719-726, 2005), which is an antibody directed against an epitope in the A antigenic site of F-glycoprotein present in a respiratory syncytial virus (RSV) envelope.
U.S. Pat. No. 6,818,216 discloses novel anti-RSV antibodies which can permit administration of lower dosages owing to their superior affinities, compared to conventional anti-RSV antibodies.
However, these antibodies have fundamental problems in that variation in the antigen structure of genes by mutants inhibits the antibody from recognizing the antigen any more, thus making it impossible to realize antiviral activity of the antibody specific for the antigen.
The reason for such a problem is that developments of antiviral antibodies are targeted on viral gene products. An alternative to solve this problem is to develop viral nucleic acid-targeting antibodies. However, there is no antibody associated with the alternative reported to date. A nuclease was reported as an enzyme degrading nucleic acid. The nuclease transferred into host cells is very cytotoxic to the cells and thus causes the fundamental problem of cell death. Such a problem inevitably restricts the developments of viral nucleic acid-targeting antibodies.
Meanwhile, there are only a few of antibody proteins known as catalytic antibodies that bind to antigens and at the same time exhibit enzymatic activities on the antigens. Some anti-DNA, anti-RNA and anti-DNA/RNA antibodies are known as naturally-generating catalytic antibodies (Buneva, et al., Appl Biochem Biotechnol 75: 63-76, 1998; Jang, et al, cell Mol Life Sci 60:309-320, 2003).
In addition, the only anti-DNA catalytic antibody known in the art is BV04-01 that has a structure based on recombinant single-chain variable fragment (scFv) and exhibits catalytic activity as an anti-DNA catalytic antibody degrading single- and double-strand DNAs (Gololobov, et al., Mol Immunol 34:1083-1093, 1997).
However, RNase activity, anti-virus activity on animal cells and protection possibility of self-derived nucleic acid of BV04-01 were not reported at all.